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May 1, 2008

The Corneal Epithelial Stem Cell Puzzle: What Future Discoveries Lie on the Horizon?

Arch Ophthalmol. 2008;126(5):725-726. doi:10.1001/archopht.126.5.725

Since 1986, when the “presumed corneal epithelial stem cell (CESC) location in mice” was first described by Sun and colleagues,1 we ophthalmologists have witnessed a long and exciting history of investigation into the exact location of CESC. The results of this extensive amount of cutting-edge research have led to phenomenal correspondent advancements in the basic understanding of devastating ocular surface disorders and clinical applications for tissue engineering and regenerative medicine. Thanks to the fascinating findings reported by epithelial biologists worldwide who used convincing experimental techniques, such as unique keratin expression and slow-cycling cell labeling using mouse models,2 it has now been elucidated that CESC are located in the limbal region. Initially, most researchers thought that limbal epithelial basal cells (LEBC) were, in fact, CESC; however, it was discovered that only 1% to 2% of LEBC are CESC. Interestingly, it has been shown through a refined side-population cell–sorting technique, immunohistochemical markers for putative stem cells, and clonal analysis that this also holds true for human CESC.3,4 By definition, a stem cell is “a cell that can continuously produce unaltered daughters and has the ability to produce daughter cells that have different, more restricted properties.”5 However, it is widely known that CESC only differentiate into corneal epithelial cells, not into conjunctival epithelial cells, and are therefore cells that are committed to the cornea. Thus, the concept and term stem cells as it applies to the corneal epithelium is slightly different from those associated with hematopoietic stem cells, neural stem cells, embryonic stem cells, and induced pluripotent stem cells.6 In fact, human CESC tend to exhibit unipotential cellular differentiation toward corneal-epithelial progenitor cells, transient amplifying (TA) cells, and terminal differentiated cells.

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